Notable trials of blinatumomab in pediatric patients with B-cell ALL
| Study (enrollment period) . | N . | Population . | End points . | Outcome . |
|---|---|---|---|---|
| R/R B-ALL | ||||
| Von Stackelberg et al5 Phase 1/2, single arm (Jan 2012 to Jun 2014) | 49 Ph1 44 Ph2 | Aged <18 years with R/R B-ALL and >25% marrow blasts | Ph1: maximum-tolerated dosage Ph2: CR rate within 2 cycles | Ph1: dosing of 5 μg/m2 per day × 1 week followed by 15 μg/m2 per day for remainder of cycle Ph2: CR 39% (95% CI, 27-51) within first 2 cycles |
| Locatelli et al6,7 Expanded access, single arm (Jan 2015 to Jul 2018) | 110 | Aged >28 days to <18 years with R/R B-ALL and ≥5% blasts or <5% blasts with MRD level ≥10−3 | Primary: incidence of adverse events Secondary: CR and MRD response (<10−4) within first 2 cycles | Grade ≥3 CRS: 1.8%; grade ≥3 neurologic events: 3.6% CR: 63% achieved CR; of these, 83% with MRD response |
| Locatelli et al8,9,∗ Phase 3, randomized (Nov 2015 to Jul 2019) | 108 | Aged >28 days to <18 years with HR first relapse B-ALL | Primary: EFS Secondary: OS | EFS: 69% for blinatumomab vs 43% for chemotherapy, P < .001; median follow-up of 22.4 months OS Hazard Ratio: 0.43 (95% CI, 0.18-1.01); median follow-up of 19.5 months |
| Brown et al10,∗ Phase 3, randomized (Dec 2014 to Sep 2019) | 208 HR/IR | Aged 1-30 years with HR or IR first relapse B-ALL | Primary: DFS Secondary: OS | 2-year DFS: 54.4% for blinatumomab vs 39.0% for chemotherapy; Hazard Ratio, 0.70 (95% CI, 0.47-1.03), 1-sided P = .03 2-year OS: 71.3% for blinatumomab vs 58.4% for chemotherapy; Hazard Ratio, 0.62 (95% CI, 0.39-0.98), 1-sided P = .02 |
| Hogan et al11 Phase 3, randomized (Dec 2014 to Sep 2019) | 255 LR | Aged 1-30 years with LR first relapse B-ALL | Primary: DFS Secondary: OS | 4-year DFS: 61.2% ± 5.0% for blinatumomab vs 49.5% ± 5.2% for chemotherapy; P = .089 4-year OS: 90.4% ± 3.0% for blinatumomab vs 79.6% ± 4.3% for chemotherapy; P = .11 |
| Newly diagnosed B-ALL | ||||
| Van der Sluis et al12 Phase 2, single arm (Jul 2018 to Jul 2021) | 30 | Aged <1 year with KMT2Ar ALL | Primary: toxic effects Secondary: MRD response (<5 × 10−4) | No clinically relevant toxic effects occurred. MRD response: 93% after blinatumomab |
| Gupta et al13,∗ Phase 3, randomized (Jul 2019 to Jun 2024) | 1440 | Aged 1-10 years with NCI SR B-ALL, with average or higher risk of relapse | Primary: DFS | 3-year DFS: 96.0% ± 1.2% for blinatumomab vs 87.9% ± 2.1% with chemotherapy; P < .001 |
| Study (enrollment period) . | N . | Population . | End points . | Outcome . |
|---|---|---|---|---|
| R/R B-ALL | ||||
| Von Stackelberg et al5 Phase 1/2, single arm (Jan 2012 to Jun 2014) | 49 Ph1 44 Ph2 | Aged <18 years with R/R B-ALL and >25% marrow blasts | Ph1: maximum-tolerated dosage Ph2: CR rate within 2 cycles | Ph1: dosing of 5 μg/m2 per day × 1 week followed by 15 μg/m2 per day for remainder of cycle Ph2: CR 39% (95% CI, 27-51) within first 2 cycles |
| Locatelli et al6,7 Expanded access, single arm (Jan 2015 to Jul 2018) | 110 | Aged >28 days to <18 years with R/R B-ALL and ≥5% blasts or <5% blasts with MRD level ≥10−3 | Primary: incidence of adverse events Secondary: CR and MRD response (<10−4) within first 2 cycles | Grade ≥3 CRS: 1.8%; grade ≥3 neurologic events: 3.6% CR: 63% achieved CR; of these, 83% with MRD response |
| Locatelli et al8,9,∗ Phase 3, randomized (Nov 2015 to Jul 2019) | 108 | Aged >28 days to <18 years with HR first relapse B-ALL | Primary: EFS Secondary: OS | EFS: 69% for blinatumomab vs 43% for chemotherapy, P < .001; median follow-up of 22.4 months OS Hazard Ratio: 0.43 (95% CI, 0.18-1.01); median follow-up of 19.5 months |
| Brown et al10,∗ Phase 3, randomized (Dec 2014 to Sep 2019) | 208 HR/IR | Aged 1-30 years with HR or IR first relapse B-ALL | Primary: DFS Secondary: OS | 2-year DFS: 54.4% for blinatumomab vs 39.0% for chemotherapy; Hazard Ratio, 0.70 (95% CI, 0.47-1.03), 1-sided P = .03 2-year OS: 71.3% for blinatumomab vs 58.4% for chemotherapy; Hazard Ratio, 0.62 (95% CI, 0.39-0.98), 1-sided P = .02 |
| Hogan et al11 Phase 3, randomized (Dec 2014 to Sep 2019) | 255 LR | Aged 1-30 years with LR first relapse B-ALL | Primary: DFS Secondary: OS | 4-year DFS: 61.2% ± 5.0% for blinatumomab vs 49.5% ± 5.2% for chemotherapy; P = .089 4-year OS: 90.4% ± 3.0% for blinatumomab vs 79.6% ± 4.3% for chemotherapy; P = .11 |
| Newly diagnosed B-ALL | ||||
| Van der Sluis et al12 Phase 2, single arm (Jul 2018 to Jul 2021) | 30 | Aged <1 year with KMT2Ar ALL | Primary: toxic effects Secondary: MRD response (<5 × 10−4) | No clinically relevant toxic effects occurred. MRD response: 93% after blinatumomab |
| Gupta et al13,∗ Phase 3, randomized (Jul 2019 to Jun 2024) | 1440 | Aged 1-10 years with NCI SR B-ALL, with average or higher risk of relapse | Primary: DFS | 3-year DFS: 96.0% ± 1.2% for blinatumomab vs 87.9% ± 2.1% with chemotherapy; P < .001 |
Dec, December; HR, high risk; IR, intermediate risk; Jan, January; Jul, July; Jun, June; LR, low risk; Nov, November; Ph1/2, Phase 1/2 clinical trial; Sep, September; SR, standard risk.
Trial terminated early because of benefit of blinatumomab.